title: Total synthesis and absolute configuration of epicoccamide D, a naturally occurring mannosylated 3-acyltetramic acid.
abstract: The endofungal metabolite epicoccamide D was synthesised in eighteen steps and 17 % yield as the first member of the family of natural glycotetramic acids. The modular character of the synthesis opens access also to analogues featuring different sugars and spacers. It comprises several high-yielding key steps. The β-D-mannosyl group was introduced by using an α-D-glucosyl imidate donor with subsequent oxidative-reductive epimerisation at C-2'. The pyrrolidine ring was closed quantitatively by a Lacey-Dieckmann condensation of an N-(β-ketoacyl)-N-methyl alaninate. The resulting 3-[ω-(β-D-mannosyl)octadec-2-enoyl]tetramic acid was hydrogenated in the presence of the rhodium catalyst (R,R)-[Rh(Et-DUPHOS)][BF4 ] to establish the (7S)-stereocentre. This was possible only after blocking the acyltetramic acid as a BF2 -chelate to prevent capture of the metal catalyst. We also assigned the hitherto unknown configuration of the natural product as being 5S,7S by comparison of its (13) C NMR spectroscopic and optical rotation data with those of our two synthetic 5S,7R/S-diasteromers.
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, NW 1, 95447 Bayreuth, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loscher
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry; D006865:Hydrogenation; D008358:Mannose / Q000737:chemistry*; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry
chemical_list: D001688:Biological Products; D006001:Glycoconjugates; D008362:Mannosides; D011760:Pyrrolidinones; C525431:epicoccamide D; C009435:tetramic acid; D012238:Rhodium; D008358:Mannose
keywords: asymmetric hydrogenation; glycoconjugates; natural products; tetramic acid; total synthesis